rs288980

Variant names:

• chr18-21029619-T-C
• rs288980
• NM_005406.3:c.1052-684A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005406.3(ROCK1):​c.1052-684A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,966 control chromosomes in the GnomAD database, including 34,816 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (34816 hom., cov: 31)
• Consequence: ROCK1 NM_005406.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742
• Publications: 9 publications found

Genes affected

ROCK1 (HGNC:10251): (Rho associated coiled-coil containing protein kinase 1) This gene encodes a protein serine/threonine kinase that is activated when bound to the GTP-bound form of Rho. The small GTPase Rho regulates formation of focal adhesions and stress fibers of fibroblasts, as well as adhesion and aggregation of platelets and lymphocytes by shuttling between the inactive GDP-bound form and the active GTP-bound form. Rho is also essential in cytokinesis and plays a role in transcriptional activation by serum response factor. This protein, a downstream effector of Rho, phosphorylates and activates LIM kinase, which in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. A pseudogene, related to this gene, is also located on chromosome 18. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROCK1	NM_005406.3	c.1052-684A>G		intron_variant	Intron 9 of 32	ENST00000399799.3	NP_005397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROCK1	ENST00000399799.3	c.1052-684A>G		intron_variant	Intron 9 of 32	1	NM_005406.3	ENSP00000382697.1
ROCK1	ENST00000635540.2	n.1052-684A>G		intron_variant	Intron 9 of 33	5		ENSP00000489185.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99460 AN: 151850 Hom.: 34743 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.633

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.655 AC: 99593 AN: 151966 Hom.: 34816 Cov.: 31 AF XY: 0.657 AC XY: 48819 AN XY: 74284

African (AFR) AF: 0.911 AC: 37808 AN: 41506

American (AMR) AF: 0.676 AC: 10317 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2027 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2569 AN: 5160

South Asian (SAS) AF: 0.598 AC: 2881 AN: 4816

European-Finnish (FIN) AF: 0.581 AC: 6126 AN: 10550

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36040 AN: 67892

Other (OTH) AF: 0.638 AC: 1338 AN: 2096

Alfa AF: 0.572 Hom.: 42005

Bravo AF: 0.673

Asia WGS AF: 0.644 AC: 2234 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs288980; hg19: chr18-18609580;